| Southern California Newspaper Calls for Greater Transparency at CIRM
February 4, 2010 at 5:50 PM
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| | Another negative newspaper editorial popped up this week concerning the California stem cell agency. The piece called for more accountability and openness on the part of $3 billion research effort. And, the editorial said, if the agency goes to court to fight reforms, lawmakers should place the proposals on a statewide ballot.The article in the Riverside Press Enterprise cited recommendations | | |
| CIRM Financially Secure Into Summer 2011
February 4, 2010 at 5:32 PM
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| | SAN FRANCISCO – Directors of the California stem cell agency today heard some good financial news – $55 million worth – that will keep them out woods through the summer of 2011.John Robson, CIRM's vice president for operations, reported that the agency has enough cash on hand to pay for its grants and operations into the first quarter of the 2010-11 fiscal year. Previously, he had predicted | | |
| In Vitro High-Capacity Assay to Quantify the Clonal Heterogeneity in Trilineage Potential of Mesenchymal Stem Cells Reveals a Complex Hierarchy of Lineage Commitment.
February 4, 2010 at 7:23 AM
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| | In Vitro High-Capacity Assay to Quantify the Clonal Heterogeneity in Trilineage Potential of Mesenchymal Stem Cells Reveals a Complex Hierarchy of Lineage Commitment. Stem Cells. 2010 Feb 1; Authors: Russell KC, Phinney DG, Lacey MR, Barrilleaux BL, Meyertholen KE, O'Connor KC In regenerative medicine, bone marrow is a promising source of mesenchymal stem cells (MSCs) for a broad range of cellular therapies. This research addresses a basic prerequisite to realize the therapeutic potential of MSCs by developing a novel high-capacity assay to quantify the clonal heterogeneity in potency that is inherent to MSC preparations. The assay utilizes a 96-well format to 1) classify MSCs according to colony-forming efficiency as a measure of proliferation capacity and trilineage potential to exhibit adipo-, chondro- and osteogenesis as a measure of multipotency, and 2) preserve a frozen template of MSC clones of known potency for future use. The heterogeneity in trilineage potential of normal bone marrow MSCs is more complex than previously reported: all eight possible categories of trilineage potential were detected. In this study, the average colony-forming efficiency of MSC preparations was 55-62%, and tripotent MSCs accounted for nearly 50% of! the colony-forming cells. The multiple phenotypes detected in this study infer a more convoluted hierarchy of lineage commitment than described in the literature. Greater cell amplification, colony-forming efficiency and colony diameter for tri- vs. unipotent clones suggest that MSC proliferation may be a function of potency. CD146 may be a marker of multipotency, with approximately 2-fold difference in mean fluorescence intensity between tri- and unipotent clones. The significance of these findings is discussed in the context of the efficacy of MSC therapies. The in vitro assay described herein will likely have numerous applications given the importance of heterogeneity to the therapeutic potential of MSCs. PMID: 20127798 [PubMed - as supplied by publisher] | | |
| European Society of Gene & Cell Therapy - 17th Annual Congress.
February 4, 2010 at 7:23 AM
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| | European Society of Gene & Cell Therapy - 17th Annual Congress. IDrugs. 2010 Feb;13(2):63-5 Authors: Chuah M The 17th Annual Congress of the European Society of Gene & Cell Therapy, held in Hanover, Germany, included topics covering new developments in the field of stem cell therapy. This conference report highlights selected presentations on stem cell gene therapy and the use of stem cells in regenerative medicine. Investigational therapies discussed include Lenti-D (Genetix Pharmaceuticals Inc/INSERM) and LentiGlobin (Genetix), a lentiviral vector-based gene transfer system containing either a human beta-globin gene or a hybrid A-gamma/beta-globin gene. PMID: 20127551 [PubMed - in process] | | |
| Pro-Inflammatory Cytokines, IFNgamma and TNFalpha, Influence Immune Properties of Human Bone Marrow and Wharton Jelly Mesenchymal Stem Cells Differentially.
February 4, 2010 at 7:23 AM
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| | Pro-Inflammatory Cytokines, IFNgamma and TNFalpha, Influence Immune Properties of Human Bone Marrow and Wharton Jelly Mesenchymal Stem Cells Differentially. PLoS One. 2010;5(2):e9016 Authors: Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB BACKGROUND: Wharton's jelly derived stem cells (WJMSCs) are gaining attention as a possible clinical alternative to bone marrow derived mesenchymal stem cells (BMMSCs) owing to better accessibility, higher expansion potential and low immunogenicity. Usage of allogenic mesenchymal stem cells (MSC) could be permissible in vivo only if they retain their immune properties in an inflammatory setting. Thus the focus of this study is to understand and compare the immune properties of BMMSCs and WJMSCs primed with key pro-inflammatory cytokines, Interferon-gamma (IFNgamma) and Tumor Necrosis Factor-alpha (TNFalpha). METHODOLOGY/PRINCIPAL FINDINGS: Initially the effect of priming on MSC mediated suppression of alloantigen and mitogen induced lymphoproliferation was evaluated in vitro. Treatment with IFNgamma or TNFalpha, did not ablate the immune-suppression caused by both the MSCs. Extent of immune-suppression was more with WJMSCs than BMMSCs in both the cases. Surprising! ly, priming BMMSCs enhanced suppression of mitogen driven lymphoproliferation only; whereas IFNgamma primed WJMSCs were better suppressors of MLRs. Further, kinetic analysis of cytokine profiles in co-cultures of primed/unprimed MSCs and Phytohematoagglutinin (PHA) activated lymphocytes was evaluated. Results indicated a decrease in levels of pro-inflammatory cytokines. Interestingly, a change in kinetics and thresholds of Interleukin-2 (IL-2) secretion was observed only with BMMSCs. Analysis of activation markers on PHA-stimulated lymphocytes indicated different expression patterns in co-cultures of primed/unprimed WJMSCs and BMMSCs. Strikingly, co-culture with WJMSCs resulted in an early activation of a negative co-stimulatory molecule, CTLA4, which was not evident with BMMSCs. A screen for immune suppressive factors in primed/unprimed WJMSCs and BMMSCs indicated inherent differences in IFNgamma inducible Indoleamine 2, 3-dioxygenase (IDO) activity, Hepatocyte growth fact! or (HGF) and Prostaglandin E-2 (PGE2) levels which could possi! bly infl uence the mechanism of immune-modulation. CONCLUSION/SIGNIFICANCE: This study demonstrates that inflammation affects the immune properties of MSCs distinctly. Importantly different tissue derived MSCs could utilize unique mechanisms of immune-modulation. PMID: 20126406 [PubMed - in process] | | |
| Changes in blood dendritic cell counts in relation to type of coronary artery disease and brachial endothelial cell function.
February 4, 2010 at 7:23 AM
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| | Changes in blood dendritic cell counts in relation to type of coronary artery disease and brachial endothelial cell function. Coron Artery Dis. 2010 Feb 1; Authors: Van Vré EA, Van Brussel I, de Beeck KO, Hoymans VY, Vrints CJ, Bult H, Bosmans JM BACKGROUND: Recently we reported a decline of circulating myeloid (m) and plasmacytoid (p) dendritic cells (DCs) in patients with coronary artery disease (CAD). This study also determined the total blood DC numbers and focused on effects of extent (one vs. three-vessel disease) and type (stable vs. unstable) of CAD, and on endothelial cell function. METHODS: Patients undergoing diagnostic coronarography were enrolled in four groups: control patients (atypical chest pain, <50% narrowing, n=15), stable one-vessel (n=15), stable three-vessel (n=15), and unstable one-vessel CAD (n=16). Total blood DCs were identified as lineage (lin) and HLADR, and DC subtypes with blood DC antigen (BDCA)-1 for mDCs and BDCA-2 for pDCs. Flow-mediated dilatation (FMD) was measured in the brachial artery. RESULTS: Numbers of total blood DCs, mDCs and pDCs declined in CAD patients compared with control patients, but without differences between the CAD groups. Interleukin-6 and high se! nsitivity C-reactive protein displayed inverse associations with mDCs. A FMD below the median of the study population, use of beta-blockers or of lipid-lowering drugs was associated with increased mDCs, whereas pDCs were similar. Interestingly, the effects of drugs and FMD were additive with that of CAD. CONCLUSION: This study indicates that lower blood DCs do not result from medication intake or endothelial dysfunction, and are an overall systemic effect of atherosclerosis rather than CAD type (stable or unstable) or number of stenotic coronary arteries. In view of discrete associations with cytokines, FMD, beta-blockers and statins, mDCs and pDCs seem to behave differently and may influence inflammation during atherosclerosis in different ways. PMID: 20124992 [PubMed - as supplied by publisher] | | |
| Human Adipose-Derived Stromal Cells Respond to and Elaborate Bone Morphogenetic Protein-2 during In Vitro Osteogenic Differentiation.
February 4, 2010 at 7:23 AM
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| | Human Adipose-Derived Stromal Cells Respond to and Elaborate Bone Morphogenetic Protein-2 during In Vitro Osteogenic Differentiation. Plast Reconstr Surg. 2010 Feb;125(2):483-93 Authors: Panetta NJ, Gupta DM, Lee JK, Wan DC, Commons GW, Longaker MT BACKGROUND:: Interest in the potential application of adipose-derived stromal cells in cell-mediated tissue engineering of bone and other mesenchymal-derived tissues is growing. This study aimed to investigate the hypothesis that human adipose-derived stromal cells respond to and elaborate bone morphogenetic protein (BMP) 2, which could represent an important target of molecular manipulation to enhance the osteogenic potential of human adipose-derived stromal cells. METHODS:: Human adipose-derived stromal cells were differentiated for 10 days toward the osteogenic lineage in osteogenic differentiation media alone or supplemented with recombinant human BMP2 (rhBMP2). Alizarin red staining was quantified by spectrophotometry. Gene expression analyses were performed using quantitative real-time polymerase chain reaction. BMP2 levels in conditioned media were titered by enzyme-linked immunosorbent assay daily during osteogenic differentiation. Human adipose-derived st! romal cells were cultured in complete or partially (50 percent) changed osteogenic differentiation media, or unchanged osteogenic differentiation media, to assay for pro-osteogenic secreted factors. In addition, human adipose-derived stromal cells were cultured in osteogenic differentiation media supplemented with BMP2/BMP4-neutralizing antibody. RESULTS:: Exogenous rhBMP2 significantly augmented the in vitro osteogenic potential of human adipose-derived stromal cells in a dose-dependent fashion, and significantly increased transcript levels of RUNX2 and osteocalcin. BMP2, BMP4, BMPR1B, and SMAD1/5 expression was significantly increased during differentiation. Enzyme-linked immunosorbent assay demonstrated significantly increased BMP2 elaboration during differentiation. Culture in conditioned osteogenic differentiation media led to significantly increased matrix mineralization. Mineralization was significantly decreased when osteogenic differentiation media was supplemented! with a BMP2/BMP4-neutralizing antibody. CONCLUSIONS:: These d! ata stro ngly support that BMP signaling is dynamic and important during normal in vitro osteogenic differentiation of human adipose-derived stromal cells. Thus, BMP2 may be used to enhance the osteogenic differentiation of human adipose-derived stromal cells for bone tissue engineering. Future studies will examine the effect of rhBMP2 on osteogenic differentiation of human adipose-derived stromal cells in vivo. PMID: 20124834 [PubMed - in process] | | |
| BMPs: From Bone to Body Morphogenetic Proteins.
February 4, 2010 at 7:23 AM
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| | BMPs: From Bone to Body Morphogenetic Proteins. Sci Signal. 2010;3(107):mr1 Authors: Obradovic Wagner D, Sieber C, Bhushan R, Börgermann JH, Graf D, Knaus P The family of bone morphogenetic proteins (BMPs) comprises approximately 30 secreted cytokines that signal through transmembrane serine/threonine kinase receptors. The BMP signaling pathways are fine-tuned on multiple levels: Extracellular antagonists modify ligand activity; several co-receptors enhance or inhibit downstream signaling events through multiple mechanisms; and intracellular molecules further regulate the signaling outcome and mediate crosstalk with other pathways. BMPs affect structures and processes throughout the entire body, ranging from embryonic patterning and development through stem cells and their niches, to tissue homeostasis and regeneration. This comprehensive involvement in various tissues had not been expected by Marshall Urist, who initially discovered the ability of an unknown factor in bone to induce bone growth in muscle and subsequently suggested the name "bone morphogenetic protein." Today, recombinant BMPs are used in clinical pra! ctice for the treatment of bone and kidney disorders, and new genetically modified BMPs are emerging as promising tools in regenerative medicine and tissue engineering. Clearly, the functions of BMPs within the body are more versatile than initially suspected. To discuss modern trends in BMP signaling, leaders in the field met for the First International BMP Workshop in Berlin in September 2009. Here, we summarize new insights on the roles of BMPs in various tissues and highlight recent findings in cell, structural, and developmental biology as well as the therapeutic potential of BMPs. Finally, we conclude that BMPs today deserve to be called body morphogenetic proteins. PMID: 20124549 [PubMed - in process] | | |
| Establishment of ERK1/2 Bistability and Sustained Activation through Sprouty 2 and its Relevance for Epithelial Function.
February 4, 2010 at 7:23 AM
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| | Establishment of ERK1/2 Bistability and Sustained Activation through Sprouty 2 and its Relevance for Epithelial Function. Mol Cell Biol. 2010 Feb 1; Authors: Liu W, Tundwal K, Liang Q, Goplen N, Rozario S, Quayum N, Gorska M, Wenzel S, Balzar S, Alam R Our objective was to establish an experimental model of a self-sustained and bistable ERK1/2 signaling process. A single stimulation of cells with cytokines causes rapid ERK1/2 activation, which returns to baseline in 4 hr. Repeated stimulation leads to sustained activation of ERK1/2 but not JNK, p38 or STAT6. The ERK1/2 activation lasts for 3-7 days and depends upon a positive feedback mechanism involving sprouty-2. Overexpression of sprouty-2 induces and its genetic deletion abrogates ERK1/2 bistability. Sprouty-2 directly activates Fyn kinase, which then induces ERK1/2 activation. A genome-wide microarray analysis shows that the bistable pERK1/2 does not induce a high level gene transcription. This is due to its nuclear exclusion and compartmentalization to Rab5+ endosomes. Cells with sustained endosomal pERK1/2 manifest resistance against growth factor withdrawal-induced cell death. They are primed for heightened cytokine production. Epithelial cells from huma! n asthma and from a mouse model of chronic asthma manifest increased pERK1/2, which is associated with Rab5+ endosomes. The increase in pERK1/2 was associated with a simultaneous increase in sprouty 2 expression in these tissues. Thus, we have developed a cellular model of sustained ERK1/2 activation, which may provide a mechanistic understanding of self-sustained biological processes in chronic illnesses such as asthma. PMID: 20123980 [PubMed - as supplied by publisher] | | |
| The relationship between temporomandibular joint pathosis and muscle tenderness in the orofacial and neck/shoulder region.
February 4, 2010 at 7:23 AM
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| | The relationship between temporomandibular joint pathosis and muscle tenderness in the orofacial and neck/shoulder region. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Jan;109(1):86-90 Authors: Inoue E, Maekawa K, Minakuchi H, Nagamatsu-Sakaguchi C, Ono T, Matsuka Y, Clark GT, Kuboki T OBJECTIVE: The objective of this study was to investigate the association between TMJ pain/disk pathosis and the muscle tenderness pattern in the orofacial and neck/shoulder region. STUDY DESIGN: One hundred seventy-one TMD patients were divided into 4 groups, including group 1: patients with painful unilateral TMJ disk displacement (DD); group 2: patients with painless unilateral TMJ DD; group 3: patients with painless bilateral TMJ DD; and group 4: patients with a bilateral normal TMJ disk position (n = 41). Each subject underwent muscle palpation and the side-by-side number of muscle tenderness points was combined as the number of muscle tenderness points on each side. Within each group, DD with and without reduction subjects were separated into subgroups and then were analyzed. RESULTS: In group 1, the median muscle tenderness points on the side with painful TMJ DD without reduction was significantly higher than on the normal side (P = .019), whereas the palpa! tion scores for painless DD patients showed no significant difference between the DD and normal sides. CONCLUSIONS: These results indicated painful disk displacement to possibly be correlated with ipsilateral muscle tenderness. PMID: 20123380 [PubMed - as supplied by publisher] | | |
| New processing approaches in calcium phosphate cements and their applications in regenerative medicine.
February 4, 2010 at 7:23 AM
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| | New processing approaches in calcium phosphate cements and their applications in regenerative medicine. Acta Biomater. 2010 Jan 29; Authors: Ginebra MP, Espanol M, Montufar EB, Perez RA, Mestres G The key feature of calcium phosphate cements (CPC) lies in the setting reaction triggered by mixing one or more solid calcium phosphate salts with an aqueous solution. Upon mixture, the reaction takes place through a dissolution-precipitation process which is macroscopically observed by a gradual hardening of the cement paste. The precipitation of hydroxyapatite nanocrystals at body or room temperature, and the fact that those materials can be used as self-setting pastes, have been for many years the most attractive features of CPC. But the need for developing materials able to sustain bone tissue ingrowth and capable of delivering drugs and bioactive molecules, together with the continuous requirement from surgeons to develop more easily handling cements has pushed the development of new processing routes that can accommodate all these requirements, taking advantage of the possibility of manipulating the self-setting CPC paste. It is the goal of this article to p! rovide a brief overview of the new processing developments in the area of CPC and to identify the most significant achievements. PMID: 20123046 [PubMed - as supplied by publisher] | | |
| Cell and drug-delivery therapeutics for controlled renal parenchyma regeneration.
February 4, 2010 at 7:23 AM
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| | Cell and drug-delivery therapeutics for controlled renal parenchyma regeneration. Adv Drug Deliv Rev. 2010 Jan 30; Authors: Minuth WW, Denk L, Glashauser A In regenerative medicine much attention is given to stem/progenitor cells for a future therapy of acute and chronic renal failure. However, up to date sound cell biological knowledge about nephron renewal in kidney is lacking. For that reason molecular mechanisms are under intense investigation leading from stem/progenitor cells to regenerated tubules. In this coherence new biomaterials and drug delivery systems have to be elaborated showing an intense stimulation on the renewal of parenchyma. To analyze tubule regeneration a powerful culture system is of fundamental importance. An advanced technique stimulates renal stem/progenitor cells to develop numerous tubules between layers of a polyester fleece. Use of chemically defined Iscove's Modified Dulbecco's Medium (IMDM) containing aldosterone (1 x 10(-7)M) results in spatial development of renal tubules within 13days of perfusion culture. Immunohistochemistry exhibits that numerous features of a polarized epithel! ium are expressed in generated tubules. Transmission electron microscopy (TEM) illuminates that generated tubules contain a polarized epithelium with a tight junctional complex and an intact basal lamina at the basal aspect. Development of tubules depends on applied aldosterone concentration and cannot be mimicked by precursors of its synthesis pathway or by other steroid hormones. Antagonists such as spironolactone or canrenoate prevent the development of tubules. This result illuminates that the tubulogenic development is mediated via the mineralocorticoid receptor (MR). Application of geldanamycin, radicicol, quercetin or KNK 437 in combination with aldosterone blocks development of tubules by disturbing the contact between MR and heat shock proteins 90 and 70. In conclusion, for the first time generation of renal tubules can be simulated under controlled in-vitro conditions. Using this model the effect of numerous innovative biomaterials and drug delivery system can be ! critically analyzed. PMID: 20122975 [PubMed - as supplied by publisher] | | |
| Treatment of acute hepatic failure in mice by transplantation of mixed microencapsulation of rat hepatocytes and transgenic human fetal liver stromal cells.
February 4, 2010 at 7:23 AM
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| | Treatment of acute hepatic failure in mice by transplantation of mixed microencapsulation of rat hepatocytes and transgenic human fetal liver stromal cells. Tissue Eng Part C Methods. 2010 Feb 2; Authors: Teng Y, Wang Y, Li S, Wang W, Gu R, Guo X, Nan X, Ma X, Pei X Microencapsulation-mediated cell therapy overcomes the immune incompatibility between donor and recipient in transplantation. The aim of this study was to investigate the effects of transplantation of microcapsules containing a mixture of rat hepatocytes and human fetal liver stromal cells, engineered to produce basic fibroblast growth factor (bFGF), on acute liver failure in mice. In vitro experiments showed that different combinations of microencapsulated rat's hepatocytes and stromal cells survive, grow and function better in 3-dimensional (3-D) conditions. The metabolic activity of rat hepatocytes co-microencapsulated with human fetal liver stromal cells, particularly when engineered to produce bFGF(FLSCs/bFGF), is significantly higher than that of microcapsules with rat hepatocytes alone. Intraperitoneal transplantation of the encapsulated hepatocytes with FLSCs/bFGF increased the survival rate and improved liver function of an acute liver failure mouse model! induced by a 70% partial hepatectomy in BALB/C mice. Moreover, dramatic liver regeneration was observed 2 days after transplantation in the group that received intraperitoneal transplantations of encapsulated hepatocytes with FLSCs/bFGF. Therefore, transplantation of encapsulated hepatocytes and human FLSCs/bFGF may be a promising strategy to treat acute liver failure or related liver diseases. PMID: 20121581 [PubMed - as supplied by publisher] | | |
| [Physiological and pathological consequences of a presence of germ line stem cells in adult tissues]
February 4, 2010 at 7:23 AM
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| | [Physiological and pathological consequences of a presence of germ line stem cells in adult tissues] Ginekol Pol. 2009 Dec;80(12):935-41 Authors: Ratajczak MZ, Machaliński B, Czajka R, Zuba-Surma E, Poziomkowska-Gesicka I, Słowik-Zyłka D Various therapheutic strategies employing stem cells have been proposed as the alternative, effective methods for therapy of multitude diseases, difficult to treat using standard, well-established methods. Advancing regenerative medicine, which is becoming a novel branch of clinical medicine, has high hopes of stem cells which could be used in treatment of injuried organs such as myocardium after heart infarction, brain after stroke, spinal cord after mechanical injury as well as in treatment of diabetes and Parkinson disease. Application of embryonic stem cells, harvested from developing embryos, is highly controversial. Hence, the stem/primitive cells isolated from adult tissuses are considered to be an optimal source of cells for therapy. Recently our research team has isolated a population of very primitive stem cells from adult tissues (very small embryonic-like stem cells - VSELs) that show several embryonic-like features. These cells can become an alternati! ve and more ethical source of the stem cells for therapy when compared to those isolated from the developing embryos. PMID: 20120940 [PubMed - in process] | | |
| The role of notch signaling in endothelial progenitor cell biology.
February 4, 2010 at 7:23 AM
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| | The role of notch signaling in endothelial progenitor cell biology. Trends Cardiovasc Med. 2009 Jul;19(5):170-3 Authors: Kwon SM, Alev C, Asahara T It is generally accepted that endothelial progenitor cells (EPCs) can promote postnatal neovascularization and be used for vascular regeneration, thus representing a promising new tool for the treatment of cardiovascular diseases. However, the exact molecular mechanisms and signaling pathways regulating the proliferation, differentiation, and migration of EPCs; their interaction with niche cells; and their regenerative capacity still remain elusive. The Notch signaling pathway shown to be important for the maintenance and differentiation of various stem and progenitor populations is also involved in EPC regulation. In this review, we will summarize the current knowledge about the pivotal role of Notch signaling in EPC biology and EPC-mediated vascular regeneration. PMID: 20005477 [PubMed - indexed for MEDLINE] | | |
| Reconstruction of an in vitro tissue-specific microenvironment to rejuvenate synovium-derived stem cells for cartilage tissue engineering.
February 4, 2010 at 7:23 AM
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| | Reconstruction of an in vitro tissue-specific microenvironment to rejuvenate synovium-derived stem cells for cartilage tissue engineering. Tissue Eng Part A. 2009 Dec;15(12):3809-21 Authors: He F, Chen X, Pei M Joint injury results in cartilage lesions that are characterized by a poor repair response. Adult stem cells are immensely appealing for biological joint repair, such as cartilage tissue engineering and regeneration. However, adult stem cells gradually lose their stemness once they are removed from their in vivo niche for plating in plastic flasks. We utilized a tissue-specific stem cell, synovium-derived stem cell (SDSC), as a model to reconstruct an in vitro three-dimensional stem cell niche. After seeding on SDSC-derived extracellular matrix, the initially wide and flat SDSCs became thin and spindle shaped and were arranged in a three-dimensional configuration with typical stem cell phenotypes. A dramatic increase in cell number and a greatly enhanced chondrogenic capacity were observed, though surprisingly the extracellular matrix-treated SDSCs did not display concomitantly improved adipogenic or osteogenic potentials. Thus, we conclude that a tissue-specific ! stem cell can be used to prepare its own in vitro niche for stem cell proliferation while maintaining and enhancing its lineage-specific stemness. The ability to reconstitute the in vitro stem cell niche will greatly benefit SDSC-based therapy for cartilage defects. PMID: 19545204 [PubMed - indexed for MEDLINE] | | |
| European Society of Gene & Cell Therapy - 17th Annual Congress.
February 4, 2010 at 6:55 AM
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| | European Society of Gene & Cell Therapy - 17th Annual Congress. IDrugs. 2010 Feb;13(2):63-5 Authors: Chuah M The 17th Annual Congress of the European Society of Gene & Cell Therapy, held in Hanover, Germany, included topics covering new developments in the field of stem cell therapy. This conference report highlights selected presentations on stem cell gene therapy and the use of stem cells in regenerative medicine. Investigational therapies discussed include Lenti-D (Genetix Pharmaceuticals Inc/INSERM) and LentiGlobin (Genetix), a lentiviral vector-based gene transfer system containing either a human beta-globin gene or a hybrid A-gamma/beta-globin gene. PMID: 20127551 [PubMed - in process] | | |
| Mesenchymal stem cell therapy for nonhealing cutaneous wounds.
February 4, 2010 at 6:55 AM
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| | Mesenchymal stem cell therapy for nonhealing cutaneous wounds. Plast Reconstr Surg. 2010 Feb;125(2):510-6 Authors: Hanson SE, Bentz ML, Hematti P SUMMARY:: Chronic wounds remain a major challenge in modern medicine and represent a significant burden, affecting not only physical and mental health, but also productivity, health care expenditure, and long-term morbidity. Even under optimal conditions, the healing process leads to fibrosis or scar. One promising solution, cell therapy, involves the transplantation of progenitor/stem cells to patients through local or systemic delivery, and offers a novel approach to many chronic diseases, including nonhealing wounds. Mesenchymal stem cells are multipotent, adult progenitor cells of great interest because of their unique immunologic properties and regenerative potential. A variety of preclinical and clinical studies have shown that mesenchymal stem cells may have a useful role in wound-healing and tissue-engineering strategies and both aesthetic and reconstructive surgery. Recent advances in stem cell immunobiology can offer insight into the multiple mechanisms ! through which mesenchymal stem cells could affect underlying pathophysiologic processes associated with nonhealing mesenchymal stem cells. Critical evaluation of the current literature is necessary for understanding how mesenchymal stem cells could potentially revolutionize our approach to skin and soft-tissue defects and designing clinical trials to address their role in wound repair and regeneration. PMID: 20124836 [PubMed - in process] | | |
| Predifferentiated adult stem cells and matrices for cardiac cell therapy.
February 4, 2010 at 6:55 AM
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| | Predifferentiated adult stem cells and matrices for cardiac cell therapy. Asian Cardiovasc Thorac Ann. 2010 Jan;18(1):79-87 Authors: Spadaccio C, Chachques E, Chello M, Covino E, Chachques JC, Genovese J Stem cell therapy is a major field of research worldwide, with increasing clinical application, especially in cardiovascular pathology. However, the best stem cell source and type with optimal safety for functional engraftment remains unclear. An intermediate cardiac precommitted phenotype expressing some of the key proteins of a mature cardiomyocyte would permit better integration into the cardiac environment. The predifferentiated cells would receive signals from the environment, thus achieving gradual and complete differentiation. In cell transplantation, survival and engraftment within the environment of the ischemic myocardium represents a challenge for all types of cells, regardless of their state of differentiation. An alternative strategy is to embed cells in a 3-dimensional structure replicating the extracellular matrix, which is crucial for full tissue restoration and prevention of ventricular remodeling. The clinical translation of cell therapy requires! avoidance of potentially harmful drugs and cytokines, and rapid off-the-shelf availability of cells. The combination of predifferentiated cells with a functionalized scaffold, locally releasing molecules tailored to promote in-situ completion of differentiation and improve homing, survival, and function, could be an exciting approach that might circumvent the potential undesired effects of growth factor administration and improve tissue restoration. PMID: 20124305 [PubMed - in process] | | |
| Persistent Donor Cell Gene Expression among Human Induced Pluripotent Stem Cells Contributes to Differences with Human Embryonic Stem Cells.
February 4, 2010 at 6:46 AM
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| | Persistent Donor Cell Gene Expression among Human Induced Pluripotent Stem Cells Contributes to Differences with Human Embryonic Stem Cells. PLoS One. 2010;5(2):e8975 Authors: Ghosh Z, Wilson KD, Wu Y, Hu S, Quertermous T, Wu JC Human induced pluripotent stem cells (hiPSCs) generated by de-differentiation of adult somatic cells offer potential solutions for the ethical issues surrounding human embryonic stem cells (hESCs), as well as their immunologic rejection after cellular transplantation. However, although hiPSCs have been described as "embryonic stem cell-like", these cells have a distinct gene expression pattern compared to hESCs, making incomplete reprogramming a potential pitfall. It is unclear to what degree the difference in tissue of origin may contribute to these gene expression differences. To answer these important questions, a careful transcriptional profiling analysis is necessary to investigate the exact reprogramming state of hiPSCs, as well as analysis of the impression, if any, of the tissue of origin on the resulting hiPSCs. In this study, we compare the gene profiles of hiPSCs derived from fetal fibroblasts, neonatal fibroblasts, adipose stem cells, and keratinocytes! to their corresponding donor cells and hESCs. Our analysis elucidates the overall degree of reprogramming within each hiPSC line, as well as the "distance" between each hiPSC line and its donor cell. We further identify genes that have a similar mode of regulation in hiPSCs and their corresponding donor cells compared to hESCs, allowing us to specify core sets of donor genes that continue to be expressed in each hiPSC line. We report that residual gene expression of the donor cell type contributes significantly to the differences among hiPSCs and hESCs, and adds to the incompleteness in reprogramming. Specifically, our analysis reveals that fetal fibroblast-derived hiPSCs are closer to hESCs, followed by adipose, neonatal fibroblast, and keratinocyte-derived hiPSCs. PMID: 20126639 [PubMed - in process] | | |
| CIRM Directors Change Big Biotech Loan Program
February 4, 2010 at 12:44 AM
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| | SAN FRANCISCO – Directors of the California stem cell agency tonight approved changes in the terms of its $500 million biotech loan program with little discussion and no dissent.Approved were the guidelines that can be found here. Elona Baum, CIRM general counsel, highlighted some of the changes from the previous loan terms. They included lowering the minimum size of a loan below $3 million under | | | |
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